We propose a five-year study to examine the relationship between alcoholism and anxiety disorders using the techniques of genetics, epidemiology, and clinical psychiatry. The basic design of the study involves a combination of the family study and high risk paradigms. By studying patterns of familial transmission of alcoholism and anxiety disorders, we will be able to confirm and extend our findings regarding the co-transmission of the two disorders among probands in treatment for depression to probands in treatment for either alcoholism or anxiety disorders as compared to normal controls. Both transmissible and non-transmissible risk factors will be identified to differentiate "pure" alcoholism from the putative form of alcoholism that is linked to anxiety. The familial transmission data will also be used to identify milder forms of manifestations of the disorders. A cohort of offspring of these proband groups who are presumed to be at increased risk for developing either alcoholism or anxiety will be studied prospectively to examine the order of presentation and the clinical course of the two disorders. The prospective design will also enable us to identify risk factors for alcoholism and the anxiety disorders without the limitation of recall bias that is often associated with retrospective studies. Specifically, in the proposed study we will: 1) obtain samples of probands with alcoholism and probands with alcoholism and anxiety disorders; 2) collect detailed information on the probands and their first-degree relatives; and 3) select and study a sample of their offspring longitudinally with intensive measurement of symptoms, diagnoses, and risk factors over the five year period. The findings derived from the proposed study may have important implications in the following areas: reducing sources of heterogeneity in alcoholism by identifying putative subtypes; specification of preclinical signs and risk factors for alcoholism; identification of susceptible persons and possible areas of intervention, with the ultimate goal of primary prevention of alcoholism.